We have found that under appropriate conditions human B-cell neoplasms can be induced to differentiate into immunoglobulin-secreting cells. This differentiation can be induced by the phorbol ester, TPA, or by the addition of both TPA and allogeneic T cells. Induction is associated with a marked change in morphology characterized by both immunoblastic and plasmacytoid features. Abundant intracytoplasmic immunoglobulin accumulation occurs and cells secrete monoclonal immunoglobulin to the culture supernatants. A variety of cell surface markers have been analyzed and a loss of surface IgD is the only significant change seen during induction. The differentiation appears to be regulated at least at a pretranslational level since there is significant and rapid accumulation of the mRNA predominantly for the secretory form rather than the membrane form of IgM. Induction of immunoglobulin secretion can be inhibited by the addition of antibody to the surface transferrin receptor OKT9.